Objective. To investigate individual variations of platelet inhibition after clopidogrel-loading doses. Setting. Department of Cardiology, Linköping University Hospital, Linköping, Sweden. Subjects. Individuals with stable angina pectoris (n ¼ 18) subject to percutaneous coronary interventions (PCI) and subsequent stenting were investigated. Methods and experimental protocol. A 300-mg clopidogrel loading dose was administrated immediately after stenting (day 1) followed by an additional 75 mg clopidogrel after 24 h (day 2). The ADP-evoked platelet fibrinogen binding was analysed to estimate platelet reactivity immediately before angiography and on day 2. A flow cytometry technique was used with two ADP solutions (final concentrations 0.6 and 1.7 lmol L )1 ) employed as platelet activating agents. Soluble P-selectin was used as a marker of platelet activity.Results. When using 1.7 lmol L )1 ADP to activate platelets four individuals had a strong inhibition (i.e. platelet reactivity <10% of the day 1-value day 2).In contrast, five patients demonstrated a weak inhibition (i.e. platelet reactivity >60% of the day 1-value day 2). Similar results were obtained when using 0.6 lmol L )1 ADP as a platelet-activating agent. Clopidogrel, however, fails to suppress platelet activity as estimated from soluble P-selectin.Conclusions. Clopidogrel evoked platelet inhibition exhibits a considerable individual heterogeneity. Some individuals only had weak responses whereas others displayed strong platelet inhibition. The present flow cytometry technique appears suitable for identifying patients with abnormal reactions after clopidogrel exposure.

Twenty-one patients with stable effort angina pectoris were randomized in a crossover study to 4 weeks traditional Chinese acupuncture or placebo tablet treatment. The patients had at least five anginal attacks per week in spite of intensive treatment. Acupuncture was given three times per week at main points Neiguan (Pericardium 6), Tongli (Heart 5), Xinshu (Urinary Bladder 15), Pishu (Urinary Bladder 20) and Zusanli (Stomach 36). Previous antianginal treatment remained unchanged during the whole study. During the acupuncture period, the number of anginal attacks per week was reduced from 10.6 to 6.1 compared with placebo (P less than 0.01). Accordingly, the performance before onset of pain during exercise test increased from 82 W to 94 W (P less than 0.05). However, maximal performance did not increase after acupuncture. Intensity of pain at maximal workload decreased from 1.4 to 0.8 (scale 0-4, P less than 0.01). Further, ST-segment depressions at maximal comparable load decreased from 1.03 to 0.71 mm after acupuncture (P less than 0.01). A life quality questionnaire confirmed improved feeling of well-being. Thus, acupuncture showed an additional beneficial effect in patients with severe, intensively treated angina pectoris.

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We have developed a rabbit model of toxic shock syndrome that uses a subcutaneous infusion pump to administer toxic shock syndrome toxin 1 (TSST-1). A dose of 150 ,ug, infused at a constant rate over a period of 7 days, resulted in a characteristic illness highlighted by fever, conjunctival hyperemia, cachexia, and lethargy. The illness was uniformly fatal, with a mean interval until death of 3.2 ± 0.4 days. Serial determinations of serum chemistries confirmed the multisystem nature of this illness. Rabbits developed profound hypocalcemia, with levels falling from 15.5 ± 0.2 to 7.6 ± 0.4 mg/dl under the influence of TSST-1. Blood urea nitrogen and creatinine rose dramatically, in the setting of oliguria or anuria. Serum glutamicpyruvic transaminase was the most reliable indicator of hepatic dysfunction, with the mean rising from 48 U/liter before administration of TSST-1 to 546 U/liter among rabbits surviving 2 days of the infusion. Creatine phosphokinase also rose dramatically in 10 of 16 rabbits. Rabbits demonstrated relative neutrophilia and lymphopenia as well as an increase in the partial thromboplastin time. Histopathologic examination demonstrated disease of multiple organs, particularly the liver, spleen, and lymph nodes, all of which demonstrated inflammation, thrombosis, hemorrhage, and erythrophagocytosis. The concurrent administration of prednisolone with TSST-1 prevented death in four of four rabbits and greatly lessened the morbidity. Rabbits were not protected from morbidity or mortality by the concurrent administration of polymyxin B. We believe that a constant, subcutaneous infusion of TSST-1 in rabbits provides a reproducible model for studying the pathogenesis of TSS.

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SummaryThereisincreasing evidence that Chlamydia pneumoniae is linked to atherosclerosis and thrombosis. In this regard, we have recentlyshown that C.pneumoniae stimulates plateletaggregation and secretion, which mayplayanimportantrole in theprogress of atherosclerosisa nd in thrombotic vascular occlusion. The aims of thep resent study were to investigate thee ffects of C. pneumoniae on platelet-mediated formation of reactive oxygen species(ROS) and oxidationoflow-density lipoprotein (LDL) in vitro.R OS production was registereda sc hanges in 2´,7`-dichlorofluorescin-fluorescence in platelets with flowc ytometry. LDL-oxidationw as determinedb ym easuring thiobarbituric acid reactive substances (TBARs). We found that C.pneumoniae stimulated plateletproduction of ROS.Polymyxin Btreatment of C. pneumoniae,b ut not elevatedt emperature,a bolishedt he stimulatory effects on plateletROS-production, which suggests that chlamydial lipopolysaccharideh as an importantr ole.I n- KeywordsAtherosclerosis, bacteria-cell interaction,o xygen radical,L PS, thrombosis hibitionofnitric oxidesynthase with nitro-L-arginine,lipoxygenasew ith 5,8,11-eicosatriynoic acid and protein kinaseCwith GF 109203X significantlylowered the production of radicals. In contrast, inhibition of NADPH-oxidase with di-phenyleneiodonium(DPI) didnot affectthe C. pneumoniae induced ROS-production.Thesefindingssuggestthat the activities of nitric oxide synthase andlipoxygenase arethe sources forROS and that the generation is dependent of theactivity of protein kinaseC.The C.pneumoniae-induced ROS-production in platelets was associatedwith an extensiveoxidationofLDL,which wassignificantly highercompared to the effect obtainedbyseparate exposureof LDLto C. pneumoniae or platelets.Inconclusion, C. pneumoniae interactionw ith platelets leading to aggregation,ROS-production and oxidativedamage on LDL, mayplayacrucial role in the developmentofatherosclerotic cardiovascular disease.

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